The importance of skin pigmentation, particularly with respect to its implications for photoprotection against skin cancers (including malignant melanoma), has resulted in a dramatic surge in research on this topic. Our laboratory continues to remain at the forefront of research on the regulation of mammalian pigmentation and focuses on characterizing: (1) pigment-related genes and their functions involved in melanocyte differentiation, (2) the biochemistry of melanins formed in the skin and their photoprotective properties, and (3) the biology of melanocyte specific differentiation antigens that serve as melanoma-specific targets. This research project is focused on characterizing parameters important to the growth, differentiation and function of normal melanocytes, and their roles in the growth and/or the metastasis of transformed melanocytes (malignant melanoma). These studies have evolved into an examination of the function and regulation of pigment-related genes, i.e. genes that encode melanocyte-specific proteins. Such proteins have generally been found to be localized in melanosomes, specific organelles that serve as the site of melanin pigment deposition; they function as catalytic and/or structural entities but perhaps more importantly, serve as specific targets of host immune responses to malignant melanoma. Our efforts in this regard have recently been targeted in 4 primary areas of interest, all of them dealing with structure, function and/or melanoma-targeting of melanosomal proteins. In the past year, we have published studies describing the interactions between fibroblasts and melanocytes that determine the relative pigmentation of the skin in various parts of the body, we have characterized the relative photoprotective properties of melanins in the skin and their effects on reducing DNA damage resulting from UV radiation, we have reported the proteomics of melanosomal proteins that can be used as specific markers of melanocytes, and we have published several papers describing the intracellular processing and trafficking of melanosomal proteins to their target organelles, which is important to the regulation of the pigmented phenotype.